The University of Michigan Multipurpose Arthritis Center Transgenic Animal Model Core provides genetically engineered mice to UM-UM-MAC investigators. Both conventional transgenic mice and mice with mutations induced by gene targeting in embryonic stem (ES) cells are produced for investigators. The Core guarantees that at least three transgenic mice will be produced for each transgene construct submitted. Core personnel provide quality tested reagents and work extensively with investigators to ensure the success for gene targeting experiments. The Core has an excellent track record. In the first four years of the preceding grant period, 687 transgenic mice were produced from 72 DNA constructs from 72 DNA constructs for 10 UM-MAC investigators. Mice with induced mutations in 12 genes were produced for 6 investigators. It is significant to note that 12 of the 13 gene targeted mice generated at the University of Michigan have been produced in the laboratories of UM-MAC investigators. Research of these animals by UM-MAC investigators has resulted in numerous publications in the fields of arthritis, musculoskeletal disease, inflammation, and gene regulation. We project that in the four years covered by the current proposal UM-MAC investigators will generate at least 80 requests for transgenic mice and 48 requests for production of germline ES cell-mouse chimeras for the generation of mouse strains with novel mutations. Dr. Sally Camper has used transgenic mice in her research since 1986 and is widely published in this field. Dr. Linda Samuelson established the technology of gene targeting in ES cells at the University of Michigan in 1990. Drs. Camper and Samuelson will work with the transgenic Core Steering Committee (composed of experienced users and a member of the UM- MAC Executive Committee) to monitor the Transgenic Core. Funding will be used to ensure that highly skilled personnel are available to meet the needs of UM-MAC investigators. Investigators will receive a 34% discount on orders for transgenic mice by pro-nuclear injection and a 34% discount on the production of gene targeted mice by blastocyst injection.